The strange tale of two mutations that nearly destroyed—then saved—a tribe of organ-eating cannibals

As anyone who’s seen a recent superhero film can tell you, mutation is an incredible thing. In the real world, mutations are just as amazing—providing the primary source of genetic variation and diversity in populations of living things. This diversity supplies the raw material for the process of evolution, which enables species to adapt to a constantly changing world.

Random changes to DNA sequences can drive the development of new traits, offer an individual innate resistance to certain diseases, or cause dramatic and life-threatening medical conditions. However, the vast majority of mutations go completely unnoticed, serving no noticeable function—positive, negative or otherwise.

On rare occasions, however, mutations can provide serendipitous protection that allows life to survive against insurmountable odds. This story follows one such occurrence, which cropped up among some lucky cannibals in the midst of a rare and deadly epidemic.

A Meal of the Dead

New Guinea. Photo by Byelikova Oksana
New Guinea. Photo by Byelikova Oksana

In the jungle strewn highlands of Papua New Guinea, a group of indigenous tribes known as the Fore people lived in relative isolation from the rest of the world until the middle of the 20th century. As Australian colonial forces penetrated deeper into the interior of the island throughout the 1950s, building roads and conquering territory, the Fore were increasingly brought into contact with the Western world.

Among the colonizers were Australian anthropologists, who made note of the language and culture of the tribes they observed, as well as many missionaries and traders—whose goals were considerably less academic.

Of the many unique cultural traditions of the Fore people, perhaps the most surprising (to Western eyes) was their practice of eating the bodies of the dead. Upon the death of a Fore person, their female family members participated in a cannibalistic funeral rite that served to both honour the dead and feed the other members of the tribe.

Soon after death, female relatives would clean and dismember the corpse of the deceased—removing the brain, stripping the muscle from the bones, and opening the thorax and abdomen to harvest the major organs. The collected human tissue was then shared as a food source by female members of the tribe, with special regard given to the brain and vital organs, which were offered in small bits to children of both sexes.

Unfortunately for the Fore, this practice coincided with an extremely rare chance event—which some scientists estimate at ‘one in a million’ odds—resulting in a devastating epidemic that killed more than 1000 tribal members during its five-year peak, and had repercussions that have continued for nearly half a century.

Killer Proteins

Photo by NIAID / Flickr
Photo by NIAID / Flickr

The extremely rare event in question was the incorrect folding of a brain protein, a spontaneous event that occurs in roughly one person in a million each year, giving birth to an infectious agent known as a ‘prion’. Unlike other contagious sources of disease like viruses or bacteria, prions are made up of an animal’s own material, which has been altered in such a way that its very shape becomes dangerous. For this reason, prions are not recognised by an organism’s immune system, allowing them to hide in plain sight from the body’s natural defences.

Like the famous ‘ice nine’ in Kurt Vonnegut’s novel Cat’s Cradle, prions have the ability to cause related proteins they touch to fold abnormally as well. As these misfolded proteins proliferate, they cause severe brain damage, destroying neurons and creating a condition known as ‘spongiform encephalopathy’—describing the sponge-like appearance of a brain full of holes.

The most common prion disease in humans is Creutzfeldt-Jakob disease (CJD), which can (very rarely) occur spontaneously in humans. This disease is also known as ‘mad cow disease’ when it occurs in livestock, and has the potential to spread to people who eat infected meat. The United Kingdom was home to one of the worst epidemics of mad cow disease in history during the 1980s, forcing the slaughter of more than 4,000,000 cattle to bring the outbreak under control. Other common conditions caused by prions include ‘chronic wasting disease’ in deer and ‘scrapie’ in sheep, though these diseases are not considered transmissible to people.

The Birth of Kuru

Photo by eGuide Travel / Flickr
Photo by eGuide Travel / Flickr

Sometime during the first half of the 20th century in the Eastern highlands of Papua New Guinea, a member of the Fore people suffered an extremely unlucky fate, when a protein in their brain spontaneously folded abnormally.

As in CJD, this protein had contorted itself into a ‘beta-pleated sheet’, rather than the normal helix-shaped structure found in healthy individuals. Unlike CJD, however, this prion variant affected different regions of the brain and produced a new set of debilitating and ultimately fatal symptoms—giving rise to a new endemic disease known as ‘kuru’.

Like all prion diseases, kuru is caused by misfolded proteins in the brain that incite any similar proteins they encounter to adopt their beta-pleated sheet configuration. As the sheets accumulate, they clump together, forming sticky deposits known as plaques that cause shrinkage and deterioration of the brain—leading to a Swiss cheese-like state.

Under another set of circumstances, the unfortunate individual who developed the first case of kuru likely would have lived a relatively normal life for about a decade, before exhibiting a bizarre set of symptoms that culminated in their death. While their decline might have been puzzling to people around them, the disease they carried likely would have followed them into the grave. As the affected person was a member of the Fore, however, their brain and body were devoured shortly after their death—spreading their most contagious tissues among the women and children of their community.

Once a person is exposed to kuru through eating infected tissues, the disease can lay dormant for decades. Incubation periods for kuru can range from 2 to 50 years, with an average incubation of 12 years until the onset of symptoms. For this reason, a death from kuru was observed as recently as 2005, in an individual who participated in funerary cannibalism as a child.

The onset of kuru is accompanied by symptoms that include intense muscle tremors (kuru comes from the Fore word for ‘to shake’) and episodes of uncontrollable laughter. Other common symptoms include slurred speech, difficulty walking and emotional instability. Once symptoms have begun, the disease progresses rapidly, typically resulting in death within 12 months of onset. Kuru is always fatal, and there has never been a documented instance of recovery from the disease.

Mutation in the Mix

Photo by AJC / Flickr
Photo by AJC / Flickr

Fortunately for the Fore, one of nature’s most fundamental processes was already working in their favour.

At the peak of the kuru epidemic, around the time Australian colonial forces started making regular contact with the Fore people in the early 1950s, roughly two per cent of the Southern Fore population died each year from the prion disease. Given the completely fatal nature of kuru, and the practices of ritual cannibalism that so effectively spread the infectious prions throughout the community, it’s easy to imagine how such a combination could cause the total annihilation of the Fore population over several generations.

In reality, however, not all members of the Fore succumbed to the epidemic. The apparent immunity of some members of the community remained as mysterious as the origins of kuru itself, until advances in technology and genetic sampling offered a clearer picture.

Research conducted at University College London compared the stored DNA from 152 Fore people who died of kuru to 2,366 living Fore people, including some older individuals who had participated in funerary cannibalism as children. The results of these analyses revealed a previously unknown mutation dubbed ‘G127V’, which replaces a single amino acid in the chains that make up the proteins that are vulnerable to diseases like kuru.

This newly observed gene mutation, which was found in nearly two per cent of the modern Fore population that were sampled in the study, was absent from the stored DNA of people who had died from kuru. When researchers inserted the gene into the genomes of transgenic mice in the lab, G127V was found to confer complete immunity to human prion diseases in the carriers of the mutation.

Evolution Has Us Covered

In a strange parallel to the birth of kuru itself, scientists believe the protective G127V mutation likely arose spontaneously in a single Fore individual sometime during the past few hundred years. Throughout the kuru epidemic, carriers of this mutation would have been immune to the disease—greatly increasing their chances to survive long enough to reproduce, and pass the trait on to their offspring.

Had Australian colonial powers never expanded their reach to the island and subsequently banned the practice of funerary cannibalism among the Fore people, it’s possible that affected populations may have crashed and then rebounded, with widespread immunity to prion diseases.

The fact that G127V was only found in populations from the region that was most ravaged by kuru indicates that this mutation was strongly favoured by natural selection. These findings provide evidence for adaptation in a context of routine cannibalism and outbreaks of prion diseases—giving us a remarkable glimpse of rapid human evolution in action.